Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Late relapse after stopping sorafenib in allogeneic hematopoietic stem cell transplant recipients

Bone Marrow Transplantation volume 54, pages 769–771 (2019)Cite this article

Subjects

The multikinase inhibitor sorafenib has shown antileukemic effect in FLT3-mutated acute myeloid leukemia (AML); however, remission is often transient. Several investigators including our group have published long-term remissions in patients treated with sorafenib after allogeneic transplant [1,2,3,4]. Recently, the mechanism by which sorafenib is effective in this setting has been described and includes activation of interleukin (IL)-15 production in leukemia cells and increase in leukemia-reactive allogeneic CD8+ T cells [5]. While sorafenib is increasingly used post transplant in patients with fms-like tyrosine kinase 3 (FLT3)-mutated AML [6], there are no guidelines on the duration of treatment and follow-up.

We have previously published our experience with the use of sorafenib following allogeneic transplant [2]. Briefly, we described 17 patients who received sorafenib for a median of 13 months, of whom 14 reached a complete remission (CR), while 5 patients eventually developed disease progression. We observed a strong protective influence of chronic graft versus host disease (cGvHD) on sorafenib resistance (defined as morphologic or molecular relapse or progression while on sorafenib), but also significant toxicity with need for dose reduction or cessation in 8 patients. Almost 4 years later, we would like to present an update of our patient cohort and report on two cases of late relapse after stopping sorafenib.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Metzelder SK, Schroeder T, Lubbert M, Ditschkowski M, Gotze K, Scholl S, et al. Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation. Eur J Cancer. 2017;86:233–9.

    Article  CAS  Google Scholar 

  2. Tschan-Plessl A, Halter JP, Heim D, Medinger M, Passweg JR, Gerull S. Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation. Ann Hematol. 2015;94:1899–905.

    Article  CAS  Google Scholar 

  3. Sora F, Chiusolo P, Metafuni E, Bellesi S, Giammarco S, Laurenti L, et al. Sorafenib for refractory FMS-like tyrosine kinase receptor-3 (FLT3/ITD+) acute myeloid leukemia after allogenic stem cell transplantation. Leuk Res. 2011;35:422–3.

    Article  Google Scholar 

  4. Metzelder SK, Schroeder T, Finck A, Scholl S, Fey M, Gotze K, et al. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia. 2012;26:2353–9.

    Article  CAS  Google Scholar 

  5. Mathew NR, Baumgartner F, Braun L, O’Sullivan D, Thomas S, Waterhouse M, et al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018;24:282–91.

    Article  CAS  Google Scholar 

  6. Antar A, Otrock ZK, El-Cheikh J, Kharfan-Dabaja MA, Battipaglia G, Mahfouz R, et al. Inhibition of FLT3 in AML: a focus on sorafenib. Bone Marrow Transplant. 2017;52:344–51.

    Article  CAS  Google Scholar 

  7. Chen YB, Li S, Lane AA, Connolly C, Del Rio C, Valles B, et al. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for fms-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20:2042–8.

    Article  CAS  Google Scholar 

  8. Brunner AM, Li S, Fathi AT, Wadleigh M, Ho VT, Collier K, et al. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol. 2016;175:496–504.

    Article  CAS  Google Scholar 

  9. Xuan L, Wang Y, Huang F, Jiang E, Deng L, Wu B, et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018;124:1954–63.

    Article  CAS  Google Scholar 

  10. Battipaglia G, Ruggeri A, Massoud R, El Cheikh J, Jestin M, Antar A, et al. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer. 2017;123:2867–74.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, University Hospital Basel, Basel, Switzerland

    S. Gerull, A. Tschan-Plessl, R. Mathew, J. R. Passweg & J. P. Halter

  2. Division of Hematology, University Hospital Zurich, Zurich, Switzerland

    G. Nair

Authors
  1. S. Gerull
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Tschan-Plessl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Mathew
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. R. Passweg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. P. Halter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Gerull.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gerull, S., Tschan-Plessl, A., Mathew, R. et al. Late relapse after stopping sorafenib in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant 54, 769–771 (2019). https://doi.org/10.1038/s41409-018-0376-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-018-0376-1

This article is cited by

Search

Advanced search

Quick links